Flexible Surface Model for Membrane Lipid-Protein Interactions

Abstract

Membrane protein conformational changes, folding and stability, and membrane fusion may all involve elastic deformation of the bilayer. The development of solid-state deuterium NMR spectroscopy [1] provides a basis for experimentally investigating lipid structure and dynamics under external forces due to temperature, osmotic pressure, or lipid composition. Deuterium NMR relaxation illuminates long-range collective lipid interactions [1]. Non-specific properties of the bilayer play a significant role in modulating protein conformational energetics [2]. A flexible-surface model (FSM) describes the balance of curvature and hydrophobic forces in lipid-protein interactions. The FSM describes elastic coupling of membrane lipids to integral membrane proteins. Curvature and hydrophobic matching to the lipid bilayer entails a stress field that explains membrane protein activity and stability [3]. Rhodopsin provides an important example, where solid-state NMR studies [4,5] and FTIR spectroscopy [6] characterize the energy landscape of the dynamically activated receptor. Upon light activation rhodopsin becomes a sensor of negative spontaneous curvature [2]. Time-resolved UV-visible and FTIR spectroscopic studies show how membrane lipids forward or back-shift the metarhodopsin equilibrium due to chemically non-specific material properties [2]. Influences of bilayer thickness, nonlamellar-forming lipids, detergents, and osmotic stress on rhodopsin function are all explained by the new biomembrane model. By contrast, the older fluid-mosaic model including lipid rafts fails to account for such effects on membrane protein activity. According to the FSM, proteins are regulated by membrane lipids whose spontaneous curvature most closely matches the activated state within the lipid membrane. [1] M.F. Brown (1996) in Membrane Structure & Dynamics, pp. 175-252. [2] M.F. Brown (1994) Chem. Phys. Lipids 73, 159-180. [3] A.V. Botelho et al. (2006) Biophys. J. 91, 4464. [4] A.V. Struts et al. (2011) Nature Struct. Mol. Biol. 18, 392-394. [5] A.V. Struts et al. (2011) PNAS 20, 8263-8268. [6] M. Mahalingam et al. (2008) PNAS 105, 17795-17800.